Therapeutic Drug Monitoring LC/MS
Pharmacological treatments and their side effects can have an impact on the patients’ safety or life’s quality. Specifically, the so called ADME (absorption, distribution, metabolism, and excretion) of the drug can be highly influenced by the genetics, environment and administration of other drugs due to co-morbidities. Therefore, in some cases the treatment with a fixed drug dose can turn out risky for patients’ health. For this reason, the Monitoring of a drug therapy which is optimized for a specific case is necessary.
On one hand, this can be particularly needed for drugs that present a narrow therapeutic range, which can be easily exceeded causing many toxic effects and/or increasing drugdrug interactions (DDIs) (Tuzimski, et al. 2020_review). On the other hand, if the drug concentration is lower than the safety ranges the pharmacological activity might not occur.
In the light of this, Therapeutic Drug Monitoring (TDM) is a strategic way to “adjust” the treatment and the dose based on patient’s clinical case (Kuhlin_cMSpec_2018). In clinical practice, several matrices can be used for TDM: whole blood, serum, plasma, dried blood spots, oral fluid. In serum, the binding between protein and drug can occur so that only a smaller quantity remains unbound and, consequently, it is responsible for the therapeutic effect. Nevertheless, for particular patients it may be necessary to monitor the total drug concentration (Tuzimski, et al. 2020_review).
Mainly, drug metabolism take place at the hepatic level, thorough Cytochrome P-450 (CYP450) (for review, Patel 2016).
Upon metabolism the drugs are usually inactivated. However, in some cases they give rise to drug metabolites which are responsible of pharmacological activity (active metabolites). Such effect can be even higher than the one of the parent drugs. Many drugs or substances might enhance or reduce the enzymatic activity of CYP450 leading to DDIs that may result in higher toxicity or lower pharmacological activity of one of the drugs (Ref. Drug Metabolism by Jennifer Le, https://www.msdmanuals.com).
DDIs might also reduce the formation of pharmacologically active metabolites (Eliasson et al.).
Here some clinical scenarios of when TDM is required are reported:
- Appearance of toxic effects
- Co-administration of drugs
- Ephatic and renal impairments
- Changes in metabolism
- Active metabolites
- Drugs with narrow therapeutic index
- Organ transplant
- Monitoring of the adherence
(Tuzimski, et al. 2020_review).
Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques allows to analyze drugs with high selectivity and sensitivity.
For a long time, immunoassays have been chosen as methods for TDM. However, the necessity to analyze specific metabolites and to avoid non-specific interference coming from other molecules or matrix led to switch to an alternative method which provides high selectivity and sensitivity, high-quality data and reproducibility. This has been found in liquid chromatography methods coupled with UV, fluorescence detectors (FLD) or MS detectors triple quad (Mass Spectrometry).
In order to ensure accurate drug measurements and to avoid unspecific interferences, the establishment of a detection method is important. (Tuzimski, et al. 2020_review).
Eureka kits represent a valid tool for TDM.
Their advantages are listed below:
• Ready to use and CE/IVD kit
• Simple, non-critical and rapid preparative phase
• Maximum specificity
• Recovery of analytes from 90% to 100% (HPLC, GC, GS/MS) and near to 100% (LC/MS)
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